Despite the success of using PSA as a prostate cancer biomarker for more than 25 years, it is clear that we need a marker that is both specific for the disease and that can differentiate the disease with the potential to kill from that which will not result in clinical significance. Utilizing proteomics focused on the nuclear matrix, we have identified alterations associated with prostate cancer. One such change, EPCA-2 is the focus of this application. The assay which detects serum levels of EPCA-2 has been shown to be specific for the disease and is able to discriminate between disease inside the prostate at the time of surgery and disease which has spread outside of the gland. The hypothesis being evaluated in this project is that EPCA-2 can serve as a prostate cancer biomarker that can differentiate between aggressive and non-aggressive prostate cancer. The goal of this project is translation of prostate cancer biomarkers (e.g. EPCA-2) into patient care for prostate cancer within a multi-institutional SPORE platform. The following specific aims are proposed to address this hypothesis: 1) to determine the ability of EPCA-2 to differentiate between populations of Gleason score 6, 7 and 8-10 in a population of Johns Hopkins Hospital patients as well as in an inter-SPORE study; 2) to analyze if serum EPCA-2 levels can identify which men, who at the time of surgery have Gleason 7 prostate cancer and a minimum of 10 year follow-up, have biochemical recurrence (PSA) from those with non-recurrent disease. These studies will consist of sample sets both from Johns Hopkins as well as other available SPORE sample sets; and 3) to begin to determine the functional role of the EPCA-2 protein in the disease process as well as the mechanism by which it is released into the serum.